ArticleBMC structural biology2007
Distinct energetics and closing pathways for DNA polymerase beta with 8-oxoG template and different incoming nucleotides.
Article in BMC structural biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 26 citations in OpenAlex.
- Structural Insights into Phosphorylation-Mediated Polymerase Function Loss for DNA PolymeraseInternational journal of molecular sciences · 2023Article
- The two faces of DNA oxidation in genomic and functional mosaicism during aging in human neurons.Frontiers in aging · 2022Review
- Role of Electron-Driven Proton-Transfer Processes in the Ultrafast Deactivation of Photoexcited Anionic 8-oxoGuanine-Adenine and 8-oxoGuanine-Cytosine Base Pairs.Molecules (Basel, Switzerland) · 2017Article
- Insertion of oxidized nucleotide triggers rapid DNA polymerase opening.Nucleic acids research · 2016Article
- Article
- Optimal and variant metal-ion routes in DNA polymerase β's conformational pathways.Journal of the American Chemical Society · 2014Article
- How DNA polymerase X preferentially accommodates incoming dATP opposite 8-oxoguanine on the template.Biophysical journal · 2013Article
- "Gate-keeper" residues and active-site rearrangements in DNA polymerase μ help discriminate non-cognate nucleotides.PLoS computational biology · 2013Article
- Catalytic effects of mutations of distant protein residues in human DNA polymerase β: theory and experiment.Biochemistry · 2012Article
- Unfavorable electrostatic and steric interactions in DNA polymerase β E295K mutant interfere with the enzyme's pathway.Journal of the American Chemical Society · 2012Article
- Substitution of Ala for Tyr567 in RB69 DNA polymerase allows dAMP to be inserted opposite 7,8-dihydro-8-oxoguanine .Biochemistry · 2010Article
- DNA polymerase family X: function, structure, and cellular roles.Biochimica et biophysica acta · 2010Review
- Mismatched base-pair simulations for ASFV Pol X/DNA complexes help interpret frequent G*G misincorporation.Journal of molecular biology · 2008Article
- Molecular dynamics simulations of nucleic acid-protein complexes.Current opinion in structural biology · 2008Review
- Differing conformational pathways before and after chemistry for insertion of dATP versus dCTP opposite 8-oxoG in DNA polymerase beta.Biophysical journal · 2007Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
background8-Oxoguanine (8-oxoG) is a common oxidative lesion frequently encountered by DNA polymerases such as the repair enzyme DNA polymerase beta (pol beta). To interpret in atomic and energetic detail how pol beta processes 8-oxoG, we apply transition path sampling to delineate closing pathways of pol beta 8-oxoG complexes with dCTP and dATP incoming nucleotides and compare the results to those of the nonlesioned G:dCTP and G:dATPanalogues.
resultsOur analyses show that the closing pathways of the 8-oxoG complexes are different from one another and from the nonlesioned analogues in terms of the individual transition states along each pathway, associated energies, and the stability of each pathway's closed state relative to the corresponding open state. In particular, the closed-to-open state stability difference in each system establishes a hierarchy of stability (from high to low) as G:C > 8-oxoG:C > 8-oxoG:A > G:A, corresponding to -3, -2, 2, 9 kBT, respectively. This hierarchy of closed state stability parallels the experimentally observed processing efficiencies for the four pairs. Network models based on the calculated rate constants in each pathway indicate that the closed species are more populated than the open species for 8-oxoG:dCTP, whereas the opposite is true for 8-oxoG:dATP.
conclusionThese results suggest that the lower insertion efficiency (larger Km) for dATP compared to dCTP opposite 8-oxoG is caused by a less stable closed-form of pol beta, destabilized by unfavorable interactions between Tyr271 and the mispair. This stability of the closed vs. open form can also explain the higher insertion efficiency for 8-oxoG:dATP compared to the nonlesioned G:dATP pair, which also has a higher overall conformational barrier. Our study offers atomic details of the complexes at different states, in addition to helping interpret the different insertion efficiencies of dATP and dCTP opposite 8-oxoG and G.
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